The eye is often "protected" from damaging defense mechanisms brought forward for disturbances such as infection, inflammation and tumors. To accomplish this protection the ocular environment is usually non-permissive to inflammation and there is an ocular influence on systemic immune responses that ultimately could damage the eye. For example, the introduction of antigen into the anterior chamber results in the initiation of a T cell-mediated antigen-specific modulation of a systemic, cell-mediated immune response to the intracameral antigen. We have investigated relationships between the eye and the systemic immune response and have shown that (i) in adult mice an intact thymus is required for the suppression of cell-mediated immunity induced by the introduction of antigen into the anterior chamber (AC) and systemic immunization (ii) CD4-, CD8-, TCR alpha, beta+ thymocytes recovered from mice following an AC injection of antigen specifically transfer the suppression of cell-mediated immunity to naive or immunized mice, (iii) like immune suppression induced by AC injection and immunization, the suppression of cell-mediated immunity by thymocytes from AC-injected mice is effected by splenic T lymphocytes. (iv) Peripheral blood mononuclear cells from mice receiving intracameral antigen induce immunoregulatory thymocytes in recipient mice. Based on these observations we propose that the circulating cellular signal induced by intracameral antigen induces thymic immunoregulatory cells that migrate to the spleen. These recent thymic emigrants, activated by an ocular signal, induce and/or become immunoregulatory T cells that effect the regulation of cell-mediated immunity. To test this hypothesis, the Specific Aims of this application are to: (1) Define further the thymocyte-inducing "signal" produced after AC-injection of antigen. (2) Demonstrate that splenic immunoregulatory T cells induced by AC -injection of antigen are derived from and/or induced by immunoregulatory thymocytes. (3) Define the immunoregulatory mechanisms of immunoregulatory thymocytes and splenic T cells induced by AC injection of antigen. Ultimately, our studies could illuminate an oculoIthymic axis that introduces exogenous antigen to the thymus leading to the activation of immunoregulatory T cells. Understanding of this axis could impact on the management o f inflammatory eye disease, organ transplants (e.g. cornea), ocular tumors and autoimmune disease.